Melibiose permease. Catalyzes the coupled stoichiometric symport of a galactoside with a
cation (either Na+, Li+, or H+). Based on LacY, a 3-d model has been derived (Yousef and Guan, 2009). Asp55 and Asp59 are essential for Na+ binding. Asp124 may play a critical role by allowing Na+-induced conformational changes and sugar binding. Asp19 may facilitate melibiose binding (Granell et al., 2010). The alternate access mechanism fits better into a flexible gating mechanism rather than the archetypical helical rigid-
body rocker-switch mechanism (Wang et al. 2016). Crystal structures of Salmonella typhimurium MelB in two
conformations, representing an outward partially occluded and an outward
inactive state (Ethayathulla et al. 2014). MelB adopts a typical MFS fold and contains a
previously unidentified cation-binding motif. Three conserved acidic
residues form a pyramidal-shaped cation-binding site for Na+, Li+ or
H+, which is in close proximity to the sugar-binding site. Both
cosubstrate-binding sites are mainly contributed by the residues from
the amino-terminal domain (Ethayathulla et al. 2014). The Glucose Enzyme IIA protein of the PTS binds MelB either in the absence or presence of a galactoside, and binding decreases the affinity for melibiose, giving rise to inducer exclusion (Saier 1989; Hariharan and Guan 2014).

Probable fucosyl-α-1,6-N-acetylglucosamine uptake porter, AlfD (next to and in an operon with a fucosidase (AlfA) specific for this disaccharide which is present in mammalian glycoproteins, glycolipids and milk (Rodríguez-Díaz et al. 2012).

Major Facilitator Superfamily Domain containing 2A, MFSD2A (543aas, 12 TMSs). Plays a role in thermogenesis via β-adrenergic signaling. Takes up Tunicamycin (TM), a mixture of related species of nucleotide sugar analogs fatty-acylated with alkyl chains of varying lengths and degrees of unsaturation, produced by several Streptomyces species (Bassik and Kampmann, 2011; Reiling et al., 2011). It is a sodium-dependent lysophosphatidylcholine (LPC) transporter expressed at the blood-brain barrier
endothelium. It is the primary route for import of docosahexaenoic acid and other long-chain
fatty acids into foetal and adult brain, and is essential for mouse and human brain growth and
function (Quek et al. 2016). In addition to a conserved
sodium-binding site, three structural features were identified: A phosphate headgroup binding
site, a hydrophobic cleft to accommodate a hydrophobic hydrocarbon tail, and three sets of ionic
locks that stabilize the outward-open conformation. Ligand docking studies and biochemical assays
identified Lys436 as a key residue for transport. It forms a salt bridge with the negative
charge on the phosphate headgroup. Mfsd2a transports structurally related
acylcarnitines but not a lysolipid without a negative charge, demonstrating the necessity of a
negative charged headgroup interaction with Lys436 for transport. These findings support a novel
transport mechanism by which LPCs are flipped within the transporter cavity by pivoting about Lys436
leading to net transport from the outer to the inner leaflet of the plasma membrane (Quek et al. 2016).

Phloem-localized sucrose:H+ symporter, Sut1 (mediates sucrose uptake or efflux dependent on the sucrose gradient and the pmf; Carpaneto et al., 2005). Sut1 is a sucrose protein symporter. Protons can move in the absence of sucrose (Carpaneto et al., 2010), but upon addition of sucrose, it becomes a symporter. Arg-188 in the rice orthologue and homologues are essential (Sun and Ward 2012).

Melanocyte-specific antigen or melanoma antigen, MatP, Slc45a2, Aim-1, AIM1, at the mouse underwhite locus. Regulated by a melanocyte-specific transcription factor essential for pigmentation, MITF (Du and Fisher 2002). Mutations in MatP in humans cause oculocutaneous albinism type IV (OCA4), an autosomal recessive inherited disorder which is
characterized by reduced biosynthesis of melanin pigmentation in skin, hair and eyes.
The MATP protein consists of 530 amino acids which contains 12 TMSs (Kamaraj and Purohit 2016). The D93N mutation causes oculocutaneous albinism 4 (OCA4), and the L374F mutatioin
correlates with light pigmentation in European populations.
Corresponding mutations were produced in the related and
well-characterized sucrose transporter from rice, OsSUT1, and transport
activity was measured by heterologous expression in Xenopus laevis oocytes and 14C-sucrose uptake in yeast. The D93N mutant had completly lost transport activity while the L374F mutant showed a 90% decrease in
transport activity, although the substrate affinity was unaffected (Kamaraj and Purohit 2016). Mutations in MATP protein showed loss of stability and became more flexible, which alter its
structural conformation and function (Kamaraj and Purohit 2016).